Acetyl-Coenzyme A Carboxylases (ACCs, EC 6.4.1.2) catalyze the formation of malonyl-coenzyme A (CoA) and regulate fatty acid biosynthesis and oxidation (A. W. Alberts, P. R. Vagelos in The Enzymes, Ed. P. D. Boyer, Academic Press New York 1972, Vol. 6, 37-82). There are two isoforms of ACC in mammals. ACC1 or ACCα is a cytosolic enzyme, and its production of malonyl-CoA is the committed step in the biosynthesis of long-chain fatty acids. In comparison, ACC2 or ACCβ is a mitochondrial enzyme, and its malonyl-CoA product regulates fatty acid oxidation by potently inhibiting the mitochondrial enzyme carnitine palmitoyltransferase I, which transports long-chain acyl-CoAs from the cytosol to the mitochondria for oxidation (J. D. McGarry anf N. F. Brown, Eur. J. Biochem. 1997, 244, 1). Mice lacking ACC2 have a higher than normal rate of fatty acid oxidation and reduced body fat and body weight (L. Abu-Elheiga, M. M. Matzuk, K. A. H. Abo-Hashema, S. J. Wakil, Science 2001, 291, 2613-2616).
ACCβ regulates mitochondrial fatty acid oxidation (Ruderman et al., Am. J. Physiol. 276, E1-E18, 1999) and ACCβ has also been linked to various diseases (Abu-Elheiga et al., Science 291, 2613-2616, 2001). ACC inhibitors seem to be suitable for the use as medicaments, particularly for the treatment and/or prophylaxis of diseases which are related to ACCβ. Furthermore, they can be used for the treatment and/or prophylaxis of diseases which are related to reduced rates of fatty acid oxidation such as obesity, dyslipidemias and diabetes.